Epinephrine is found throughout the brainstem, hypothalamus and midbrain of animals. Epinephrine and its biosynthetic enzyme, PNMT (phenylethanol- amine Nmethyltransferase) are found in neurons originating in the medulla, although epinephrine-forming enzyme activity is also found in "non-catecholamine" neurons in the hypothalamus and in a subset of glial cells,tanycytes, which line the walls of the third ventricle. This latter pool of epinephrine forming enzyme appears to be associated with neuroendocrine processes. Our view has developed to consider PNMT-containing neurons a special subset of noradrenergic neurons. These cells innervate the locus coeruleus as well as preganglionic fibers of the adrenal mila and appear to play important regulatory roles in sensory transduction as well as maintenance of homeostatic mechanisms in response to a variety of physiological stimuli. The epinephrine content in brain is a good marker of activity of these cells, and we have used this index to study the effects of energy state, sedative hypnotic intoxication and immunological stimuli on central epinephrine containing noradrenergic neuronal activity. In addition, inhibition of epinephrine synthesis has been demonstrated to modify activity in young rats and to antagonize the sedative and intoxicating effects of ethanol and barbiturates.